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Metformin is the most widely used drug in the treatment of type 2 diabetes, the diabetes of old age. An estimated 120 million people worldwide are currently treated with metformin, making metformin one of the most globally used drugs. Despite being an old drug, first brought on the market in 1957 in Europe, it still is the first line treatment. Compared to other diabetes treatments, metformin has been shown to result in lower risk of cancer and reductions in overall mortality. Several animal studies, since the 1980s, suggest that metformin may be an anti-aging drug.
The first reports linking metformin treatment with reductions in vitamin B12 blood levels stem from the 1970s. A meta-review published earlier this year in the journal Internal and Emergency Medicine confirms that metformin use leads to lower B12 levels. Between 6 and 33% of patients treated with metformin may suffer from vitamin B12 deficiency. Long term vitamin B12 deficiency will lead to insufficient production of red blood cells (anemia), memory impairment, depression, loss of balance, and can lead to nerve damage (neuropathy). Interestingly, diabetes is also a well known risk factor for the development of neuropathy and thus the combination of diabetes with the vitamin B12 deficiency caused by metformin therapy may synergistically increase the risk for neuropathy.
Vitamin B12 deficiency is treatable, but if ignored can cause irreversible damage
Last week at the European Association for the Study of Diabetes 2015 Meeting, Mattijs Out an internist from the Netherlands warned that current guidelines for diabetes treatment do not include regular vitamin B12 blood tests or supplementation. Vitamin B12 deficiency can easily be screened for by blood tests and treatment is cheap. Early diagnosis and treatment is important because the problem is still reversible, however long-term B12 deficiency will lead to irreversible nerve damage.
Using data from the Hyperinsulinemia: the Outcomes of its Metabolic Effects (HOME) study, dr. Out found an increase in methylmalonate levels (a sensitive marker of vitamin B12 deficiency). Neuropathy scores were not different between metformin users and those given a placebo but after mathematical analysis it could be shown that this resulted from a balance between the protection offered by reducing blood glucose levels and the increased risk by reducing vitamin B12 levels. Hence prevention of vitamin B12 deficiency in metformin-treated diabetes patients could help to reduce the incidence of neuropathy.
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